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Current practices in prostate pathology reporting: results from a survey of genitourinary and general pathologists
No full textAIMS: Standardizing pathology reporting protocols through peer consensus review is critical for the best quality of care metrics. Reporting heterogeneity due to discrepancies among professional societies and practice patterns may lead to heterogeneous management and treatment approaches. This issue prompted a multi-institutional survey of pathologists to address potential similarities or differences in trends and practice patterns in prostate pathology reporting worldwide.
METHODS AND RESULTS: A REDCap survey was distributed among 175 pathologists worldwide, recruited through invitations and social media. The response rate among invited pathologists was 83%. The practice locations were as follows: North America (USA, Canada, and Mexico, 62%), Europe (17%), Australia/New Zealand (3%), Central/South America (2%), Asia (13%), and Africa (2%). Most pathologists practiced for \u3c 5 years (28%). A genitourinary (GU) pathology fellowship was completed by 37%, 58% practiced in a subspecialized setting, and 43% in academia. Reporting includes (63%) or subtracts (37%) intervening benign tissue. Both Gleason score and Grade Groups (GG)s were reported by 96% of responders, whereas 94% report percent pattern 4 (%4). Aggregate grading and volume estimation in undesignated cores with different grades in the same jar are reported by 73% and 54% for systematic biopsies, and 83% and 62% for targeted biopsies, respectively. Cribriform morphology was reported by 81%. For presumed intraductal carcinoma (IDC), 89% use basal cell markers when isolated (iIDC), 82% with GG1 cancer, and 37% with ≥GG2. iIDC or IDC associated with GG1 or with ≥GG2 was not graded by 90%, 78%, and 70%, respectively. In radical prostatectomies, 90% report %4, but only 53% report it if the overall grade is ≥7. A tumour with Gleason 3 + 3 = 6 and \u3c 5% pattern 4 was graded as GG2 by 64%. A \u3c 5% cutoff for defining tertiary pattern was used by 74%, and 80% report \u3e5% pattern 4 or 5 as a secondary pattern. Grading was assigned based on the dominant nodule by 59%. Finally, reporting practices were significantly associated with demographic characteristics.
CONCLUSIONS: Although most issues are agreed upon, significant discordance is identified among societies and pathologists in different practice settings. We hope this survey will serve as the basis for future studies and new collaborative approaches to more standardized reporting practices
Genomic profiling of urological malignancies using tissue-based next generation sequencing
No full textAdvances in understanding genomic drivers of human malignancies have evolved from morphologic evaluations to in-depth DNA and RNA analyses and gene expression profiling. In urologic malignancies, these molecular diagnostics are integral to patient management, aiding pathological diagnosis, providing prognostic and predictive relevance, and identifying therapeutic options for advanced diseases. For instance, renal cell carcinoma frequently harbors alterations in VHL, PBRM1, and BAP1, influencing therapeutic responses, while urothelial carcinoma is characterized by FGFR3 mutations and TERT promoter alterations, which have implications for targeted therapy. Prostate cancer commonly involves TMPRSS2-ERG fusions and BRCA2 mutations, affecting treatment strategies, and penile squamous cell carcinoma follows distinct HPV-dependent and HPV-independent pathways, with mutations in TP53 and CDKN2A genes. These advances in molecular pathology have deepened our understanding of these complex diseases and facilitated the introduction of novel targeted therapies. While these advances promise improved diagnosis, prognosis, and treatment options, many questions remain regarding the variable patient responses within the same histologic types. Addressing these will enable optimal management strategies and the development of personalized treatments targeting specific molecular alterations to improve patient outcomes
Partial Courses of Fidaxomicin Followed by Oral Vancomycin and the Effect on Recurrence of Clostridioides difficile Infections
No full textBACKGROUND: Clostridioides difficile infection (CDI) causes a significant national health care burden. Literature has demonstrated lower rates of CDI recurrence with fidaxomicin compared with oral vancomycin. However, patients are sometimes switched to oral vancomycin before completing a fidaxomicin course.
OBJECTIVE: The objective of this study is to evaluate rates of CDI recurrence in full courses of fidaxomicin versus partial courses of fidaxomicin followed by a switch to oral vancomycin.
METHODS: In this single-center, retrospective, cohort study of adults with CDI, patients were screened for inclusion if they received either a full 10-day course of fidaxomicin or partial course of fidaxomicin followed by a switch to oral vancomycin. The primary outcome was the rate of CDI recurrence within 30 days after completion of initial therapy determined by a positive CDI test and initiation of treatment.
RESULTS: Ninety-nine patients received a full course of fidaxomicin, and 95 patients received a partial course of fidaxomicin followed by oral vancomycin. Mean age was lower in the full course group compared with the partial course (65.3 years vs 71.5 years, P \u3c 0.002). Clostridioides difficile infection recurrence occurred in 5.1% of the full course group and 7.4% of the partial therapy group (P = 0.503) at 30 days and 13.1% versus 14.7% (P = 0.747) at 90 days. Clostridioides difficile infection-related readmissions at 30 days were similar in the full course and partial course groups (7.1% vs 4.2%, P = 0.389).
CONCLUSION AND RELEVANCE: Partial courses of fidaxomicin followed by oral vancomycin had similar 30-day CDI recurrence compared with full course fidaxomicin
An Accord Between Man and Machine: Concordance Between Traditional and Novel Mapping Techniques for Atrioventricular Nodal Reentrant Tachycardia Ablation.
No full textIntroduction: Catheter ablation has evolved rapidly, starting with conventional anatomic techniques, followed by electrogram mapping, and now isochronal late activation mapping techniques are currently in practice. Success rates of ablation were higher with electrogram mapping compared to conventional anatomic mapping. Conventional techniques performed by an experienced operator have not previously been compared to novel mapping techniques in this cohort.
Methods: A total of 14 consecutive patients underwent Atrioventricular Nodal Reentry Tachycardia (AVNRT) (supraventricular tachycardia with ventriculoatrial (VA) interval \u3c 70 ms) ablations, where the operator predicted slow and fast pathway collision points, and a sinus collision mapping was also obtained. Ablation was performed with the operator blinded to mapping. Criteria for successful prediction were an ablation point within 4 mm of machine prediction, with a post-ablation junctional response; slow pathway elimination, confirmed by the absence of an Atrio-His jump with or without an echo beat; and non-inducibility of AVNRT. Other secondary outcomes included age, sex, total radiofrequency (RF) ablation time, number of RF applications, total fluoroscopy time, dose, and other postoperative complications or death.
Results: Operator prediction of sinus collision location coincided with machine prediction in 85.7% of cases. Regarding patient demographics, 57% of the population were female, with a mean age of 60 years. The average distance from operator prediction to machine prediction was 1.75 mm. The percentage of junctional rhythm post-ablation in concordant patients was 83.3%. The mean ablation time was 97 seconds, with seven RF applications on average. Fluoroscopy was used in two patients, with minimal exposure. No post-procedure complications, such as pericardial effusion or atrioventricular (AV) block, were noted.
Conclusion: Conventional techniques were not previously compared with novel mapping techniques. In our retrospective cohort study, there was a concordance of 85.7% between an experienced operator and an algorithm-predicted model. The distance between predicted and actual ablation points was close. Although no concrete predictions can be made given our limited retrospective data, with many limitations, novel mapping techniques are useful tools that currently supplement AVNRT ablations and will likely play a crucial role in the future
Rapid Onset of Itch Relief With Tapinarof in Two Phase 3 Trials in Atopic Dermatitis
No full textBACKGROUND: In the ADORING 1 and 2 phase 3 trials, tapinarof cream 1% once daily (QD) demonstrated significant efficacy and was well tolerated in adults and children down to 2 years of age with atopic dermatitis (AD). Here we evaluate the time to onset of itch relief in the trials.
METHODS: Eight hundred thirteen (813) patients were randomized to tapinarof cream 1% or vehicle QD for 8 weeks. Pruritus relief was assessed by Peak Pruritus Numerical Rating Scale (PP-NRS) scores (daily and by visit at weeks 1, 2, 4, and 8).
RESULTS: Mean baseline PP-NRS scores in ADORING 1 and 2 were 6.7 and 6.8, respectively. Greater reductions in mean daily PP-NRS scores were observed for tapinarof vs vehicle as early as day 1, 24 hours after initial application (-1.2 vs -1.0; pooled post hoc analysis), with significant improvements at day 2 (-1.6 vs -1.1, P=0.0115). Daily pruritus improvements continued through week 8. Significantly greater reductions in mean weekly PP-NRS scores with tapinarof vs vehicle were demonstrated at week 1 in ADORING 1, -2.0 vs -1.2 (P\u3c 0.0001) and ADORING 2, -2.0 vs -1.3 (P=0.0010), continuing through week 8, -4.1 vs -2.6 and -4.1 vs -2.4 (both P\u3c 0.0001).
CONCLUSION: Tapinarof demonstrated rapid and clinically meaningful pruritus relief in patients with AD, with improvements starting 24 hours after initial application and statistically significant improvements at day 2.
CITATION: Simpson EL, Silverberg JI, Bissonnette R, et al. Rapid onset of itch relief with tapinarof in two phase 3 trials in atopic dermatitis. J Drugs Dermatol. 2025;24(6):600-607. doi:10.36849/JDD.8860R1
Novel insights into beta cell ER stress CHOP and its role in HFpEF development
No full textINTRODUCTION: Heart failure with preserved ejection fraction (HFpEF) is a multifactorial cardiovascular disorder characterized by diastolic dysfunction and often associated with hypertension and metabolic disturbances. We aimed to determine the inter-relationship between C/EBP homologous protein (CHOP) in b-cells and HFpEF development.
METHODS: Eight-week-old male mice b-cell(flox/flox) and b-cell(CHOP-/-) were randomly divided into four groups: control b-cell(flox/flox) and b-cell(CHOP-/-) mice subjected to standard diet and water. b -cell(flox/flox) and b-cell(CHOP-/-) mice fed a high-fat diet (HFD) and L-NAME (0.5 g/L) for five weeks. A comprehensive cardiovascular, metabolic, and histological evaluation was conducted.
RESULTS: Following five weeks of HFD and L-NAME, b-cell(flox/flox) mice exhibited clinical and molecular manifestations of HFpEF. These include diastolic dysfunction, a normal cardiac ejection fraction, hypertension, metabolic disorders, cardiac hypertrophy with fibrosis, pulmonary edema, renal injury, and reduced exercise tolerance. Vascular endothelial dysfunction was also observed. Western blot analysis showed a reduced phosphorylated endothelial nitric oxide synthase in mesenteric resistance arteries (MRA), concomitant with qRT-PCR data revealing elevated inflammatory and unfolded protein response markers in MRA, heart, and pancreas. Interestingly, b-cell(CHOP-/-) mice subjected to an HFD and L-NAME were protected from HFpEF and its associated pathologies. These mice displayed improved cardiac and vascular endothelial function, exercise tolerance, and reduced unfolded protein response and inflammatory factors compared to their b-cell(flox/flox).
CONCLUSION: Our research indicates that deleting the unfolded protein response CHOP in b-cells has a robust cardiovascular protective effect against HFpEF pathogenesis. Therefore, targeting CHOP in b-cells is a promising lead for HFpEF pathogenesis therapy
Cultivating Nurse Leaders: Integrating Policy Analysis Projects in Doctor of Nursing Practice Programmes
No full textAIM: To present the process of establishing a Doctor of Nursing Practice (DNP) policy analysis project option at one nursing school, offering examples of diverse student and graduate analyses to guide other institutions.
BACKGROUND: Nurses are skilled patient advocates, and their advocacy forms a crucial foundation for influencing health policy. This, in turn, enhances population health and addresses health disparities, particularly for vulnerable groups. DNP students are educated to use innovative methods to integrate current evidence to inform practice and policy, yet some nursing schools lack resources to support comprehensive DNP policy analysis projects.
METHODS: The article presents a case example of how one institution developed a pathway and instructional support to formally offer DNP students the option to perform a DNP policy analysis project.
DISCUSSION: Essential elements to support students\u27 successful completion of a DNP policy analysis project include adequate faculty expertise in health policy and a structured institutional framework. Residency activities must deepen a student\u27s understanding and knowledge about policy and the health problem trying to be solved with policy. Clear documentation of these unique residency activities is crucial. There is a strong emphasis on the need for clear communication and guidance between programme faculty, programme mentors and students. DNP policy analysis projects enrich students\u27 knowledge, skills and networks, fostering future policy leaders and facilitating collaboration with clinical experts across diverse research fields.
CONCLUSION: Nurturing DNP students completing policy analysis projects is vital for translating evidence into practice, developing future nurse policy leaders and ensuring health equity and access to quality healthcare.
IMPLICATIONS FOR THE PROFESSION AND PATIENT CARE: DNP policy projects can positively influence nursing practice and policy. Expanding upon previous DNP students\u27 policy analysis projects also provides a unique opportunity to build and broaden nursing\u27s impact on policy development
Safety and efficacy of docosahexaenoic acid supplementation during neoadjuvant breast cancer therapy: Findings from the phase II, double-blind, randomized controlled DHA-WIN trial
No full textThere is limited clinical evidence of docosahexaenoic acid (DHA) efficacy during breast cancer neoadjuvant chemotherapy (NAC). This randomized, double-blind, placebo-controlled trial aimed to investigate the safety and efficacy of DHA supplementation in breast cancer patients undergoing NAC. Participants (n = 49) were assigned to receive either DHA 4.4 g/day orally (algae triacylglycerol) or a placebo (corn/soy oil) over six cycles (18 weeks) of NAC. The primary outcome was the evaluation of changes in the percentage of Ki-67 expression, assessed by immunohistochemistry analysis from pre- to post-treatment. Secondary outcomes included pathological complete response, incidence of adverse effects, and 3-year survival analysis. Compliance was evaluated by fatty acid analysis of plasma phospholipids and erythrocyte total lipids quantified by gas-liquid chromatography. The expression of Ki-67 significantly decreased in both groups, with no significant effects of the DHA intervention (p = 0.38). When stratified by breast cancer subtype, there was a trend of greater reduction in Ki-67 expression in the human epidermal growth receptor 2 (HER2+++) subtype in the DHA group compared to placebo (p = 0.1). The % of DHA in erythrocytes and plasma phospholipids was increased by two-fold at 9 and 15 weeks of therapy in the DHA group, while it remained unchanged in the placebo group (p-interaction \u3c 0.001). There was no reported incidence of adverse effects related to the intervention, and no significant effects were found in the other secondary outcomes. NAC significantly decreased the expression of Ki-67, with no additional beneficial effects observed by DHA supplementation. Further research is necessary to confirm these findings
Transcriptome analysis and artificial intelligence for predicting lymph node metastasis of esophageal squamous cell carcinoma
No full textBACKGROUND: Lymph node metastasis (LNM) is the most common route of metastasis in esophageal squamous cell carcinoma (ESCC), and the treatment of patients with ESCC largely depends on the LNM status. The methods for diagnosing LNM in ESCC are still not accurate enough, and accurate LNM staging is crucial for clinical practice. The purpose of this study was to investigate the value of combining transcriptome analysis with artificial intelligence (AI) in predicting LNM and to construct an effective predictive model for LNM in ESCC.
METHODS: We first enrolled 36 patients with ESCC for RNA sequencing (RNA-seq) to identify the differentially expressed messenger RNA (mRNAs), and then selected candidate genes via a random forest machine learning algorithm. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of three candidate genes. For the assessment of the overall survival (OS) of patients with ESCC, we used the Kaplan-Meier method and the log-rank test. Univariate and multivariate logistic regression analyses were performed to screen for risk model factors. The model was validated with the area under the curve (AUC) and visualized through a nomogram. For AI model building, random forest was conducted. We included five variables to create the AI model, and divided the data from 209 patients into a training set and a validation set to evaluate the model\u27s performance. Thereafter, receiver operating characteristic (ROC) curves and the AUC were used to validate the AI system and to conduct subgroup analyses.
RESULTS: RNA-seq identified 2,837 genes that were differentially expressed in ESCC tissues with LNM. We used a random forest machine learning algorithm to eliminate candidate diagnostic genes for patients with ESCC with LNM, with the three most diagnostic genes being SIM2, CUX1, and CYP4B1. Analysis of OS indicated that patients with LNM had a worse prognosis. Low expression levels of SIM2 were negatively correlated with OS. However, high expression levels of CUX1 or CYP4B1 were negatively correlated with OS. We added five independent influencing factors to the risk model via univariate and multivariate logistic regression analyses. In the ROC curve analysis, the AUC for the most effective logistic regression model was 0.83. A nomogram was used to display the predictive variables. Finally, these five variables were used to create the AI model, and the AUC was 0.78. Moreover, the subgroup analysis indicated that the AI model that incorporated only the T3 clinical tumor stage yielded an AUC of 0.78.
CONCLUSIONS: AI and transcriptome analysis can be used to create a risk model for predicting LNM, and it can enhance prediction accuracy and inform clinical staging and decision-making before surgery